The deadly VEXAS syndrome is more common than doctors thought

A mysterious new disease may be to blame for severe, unexplained inflammation in older men. Now, researchers have their first good look at who the disease strikes, and how often.

VEXAS syndrome, an illness discovered just two years ago, affects nearly 1 in 4,000 men over 50 years old, scientists estimate January 24 in JAMA. The disease also occurs in older women, though less frequently. Altogether, more than 15,000 people in the United States may be suffering from the syndrome, says study coauthor David Beck, a clinical geneticist at NYU Langone Health in New York City. Those numbers indicate that physicians should be on the lookout for VEXAS, Beck says. “It’s underrecognized and underdiagnosed. A lot of physicians aren’t yet aware of it.”
Beck’s team reported discovering VEXAS syndrome in 2020, linking mutations in a gene called UBA1 to a suite of symptoms including fever, low blood cell count and inflammation. His team’s new study is the first to estimate how often VEXAS occurs in the general population — and the results are surprising. “It’s more prevalent than we suspected,” says Emma Groarke, a hematologist at the National Institutes of Health in Bethesda, Md., who was not involved with the study.
VEXAS tends to show up later in life ­­— after people somehow acquire UBA1 mutations in their blood cells. Patients may feel overwhelming fatigue, lethargy and have skin rashes, Beck says. “The disease is progressive, and it’s severe.” VEXAS can also be deadly. Once a person’s symptoms begin, the median survival time is about 10 years, his team has found.

Until late 2020, no one knew that there was a genetic thread connecting VEXAS syndrome’s otherwise unexplained symptoms. In fact, individuals may be diagnosed with other conditions, including polyarteritis nodosa, an inflammatory blood disease, and relapsing polychondritis, a connective tissue disorder, before being diagnosed with VEXAS.

To ballpark the number of VEXAS-affected individuals, Beck’s team combed through electronic health records of more than 160,000 people in Pennsylvania, in a collaboration with the NIH and Geisinger Health. In people over 50, the disease-causing UBA1 mutations showed up in roughly 1 in 4,000 men. Among women in that age bracket, about 1 in 26,000 had the mutations.

A genetic test of the blood can help doctors diagnose VEXAS, and treatments like steroids and other immunosuppressive drugs, which tamp down inflammation, can ease symptoms. Groarke and her NIH colleagues have also started a small phase II clinical trial testing bone marrow transplants as a way to swap patients’ diseased blood cells for healthy ones.

Beck says he hopes to raise awareness about the disease, though he recognizes that there’s much more work to do. In his team’s study, for instance, the vast majority of participants were white Pennsylvanians, so scientists don’t know how the disease affects other populations. Researchers also don’t know what spurs the blood cell mutations, nor how they spark an inflammatory frenzy in the body.

“The more patients that are diagnosed, the more we’ll learn about the disease,” Beck says. “This is just one step in the process of finding more effective therapies.”

Too much of this bacteria in the nose may worsen allergy symptoms

A type of bacteria that’s overabundant in the nasal passages of people with hay fever may worsen symptoms. Targeting that bacteria may provide a way to rein in ever-running noses.

Hay fever occurs when allergens, such as pollen or mold, trigger an inflammatory reaction in the nasal passages, leading to itchiness, sneezing and overflowing mucus. Researchers analyzed the composition of the microbial population in the noses of 55 people who have hay fever and those of 105 people who don’t. There was less diversity in the nasal microbiome of people who have hay fever and a whole lot more of a bacterial species called Streptococcus salivarius, the team reports online January 12 in Nature Microbiology.
S. salivarius was 17 times more abundant in the noses of allergy sufferers than the noses of those without allergies, says Michael Otto, a molecular microbiologist at the National Institute of Allergy and Infectious Diseases in Bethesda, Md. That imbalance appears to play a part in further provoking allergy symptoms. In laboratory experiments with allergen-exposed cells that line the airways, S. salivarius boosted the cells’ production of proteins that promote inflammation.

And it turns out that S. salivarius really likes runny noses. One prominent, unpleasant symptom of hay fever is the overproduction of nasal discharge. The researchers found that S. salivarius binds very well to airway-lining cells exposed to an allergen and slathered in mucus — better than a comparison bacteria that also resides in the nose.

The close contact appears to be what makes the difference. It means that substances on S. salivarius’ surface that can drive inflammation — common among many bacteria — are close enough to exert their effect on cells, Otto says.

Hay fever, which disrupts daily activities and disturbs sleep, is estimated to affect as many as 30 percent of adults in the United States. The new research opens the door “to future studies targeting this bacteria” as a potential treatment for hay fever, says Mahboobeh Mahdavinia, a physician scientist who studies immunology and allergies at Rush University Medical Center in Chicago.

But any treatment would need to avoid harming the “good” bacteria that live in the nose, says Mahdavinia, who was not involved in the research.

The proteins on S. salivarius’ surface that are important to its ability to attach to mucus-covered cells might provide a target, says Otto. The bacteria bind to proteins called mucins found in the slimy, runny mucus. By learning more about S. salivarius’ surface proteins, Otto says, it may be possible to come up with “specific methods to block that adhesion.”

Lots of Tatooine-like planets around binary stars may be habitable

SEATTLE — Luke Skywalker’s home planet in Star Wars is the stuff of science fiction. But Tatooine-like planets in orbit around pairs of stars might be our best bet in the search for habitable planets beyond our solar system.

Many stars in the universe come in pairs. And lots of those should have planets orbiting them (SN: 10/25/21). That means there could be many more planets orbiting around binaries than around solitary stars like ours. But until now, no one had a clear idea about whether those planets’ environments could be conducive to life. New computer simulations suggest that, in many cases, life could imitate art.
Earthlike planets orbiting some configurations of binary stars can stay in stable orbits for at least a billion years, researchers reported January 11 at the American Astronomical Society meeting. That sort of stability, the researchers propose, would be enough to potentially allow life to develop, provided the planets aren’t too hot or cold.

Of the planets that stuck around, about 15 percent stayed in their habitable zone — a temperate region around their stars where water could stay liquid — most or even all of the time.

The researchers ran simulations of 4,000 configurations of binary stars, each with an Earthlike planet in orbit around them. The team varied things like the relative masses of the stars, the sizes and shapes of the stars’ orbits around each other, and the size of the planet’s orbit around the binary pair.

The scientists then tracked the motion of the planets for up to a billion years of simulated time to see if the planets would stay in orbit over the sorts of timescales that might allow life to emerge.

A planet orbiting binary stars can get kicked out of the star system due to complicated interactions between the planet and stars. In the new study, the researchers found that, for planets with large orbits around star pairs, only about 1 out of 8 were kicked out of the system. The rest were stable enough to continue to orbit for the full billion years. About 1 in 10 settled in their habitable zones and stayed there.

Of the 4,000 planets that the team simulated, roughly 500 maintained stable orbits that kept them in their habitable zones at least 80 percent of the time.

“The habitable zone . . . as I’ve characterized it so far, spans from freezing to boiling,” said Michael Pedowitz, an undergraduate student at the College of New Jersey in Ewing who presented the research. Their definition is overly strict, he said, because they chose to model Earthlike planets without atmospheres or oceans. That’s simpler to simulate, but it also allows temperatures to fluctuate wildly on a planet as it orbits.
“An atmosphere and oceans would smooth over temperature variations fairly well,” says study coauthor Mariah MacDonald, an astrobiologist also at the College of New Jersey. An abundance of air and water would potentially allow a planet to maintain habitable conditions, even if it spent more of its time outside of the nominal habitable zone around a binary star system.

The number of potentially habitable planets “will increase once we add atmospheres,” MacDonald says, “but I can’t yet say by how much.”

She and Pedowitz hope to build more sophisticated models in the coming months, as well as extend their simulations beyond a billion years and include changes in the stars that can affect conditions in a solar system as it ages.

The possibility of stable and habitable planets in binary star systems is a timely issue says Penn State astrophysicist Jason Wright, who was not involved in the study.

“At the time Star Wars came out,” he says, “we didn’t know of any planets outside the solar system, and wouldn’t for 15 years. Now we know that there are many and that they orbit these binary stars.”

These simulations of planets orbiting binaries could serve as a guide for future experiments, Wright says. “This is an under-explored population of planets. There’s no reason we can’t go after them, and studies like this are presumably showing us that it’s worthwhile to try.”